IK-175 + nivolumab

IK-175 + nivolumab is a combination therapy under investigation for the treatment of advanced cancers, particularly urothelial carcinoma and head and neck squamous cell carcinoma. IK-175 is an oral, selective small molecule inhibitor of the Aryl Hydrocarbon Receptor (AHR), a ligand-activated transcription factor implicated in promoting an immunosuppressive tumor microenvironment by binding kynurenine. This immunosuppression may drive resistance to immune checkpoint inhibitors such as PD-1/PD-L1 inhibitors. Nivolumab is a fully human monoclonal antibody that targets programmed cell death protein 1 (PD-1) on T-cells, blocking its interaction with PD-L1/PD-L2 and restoring anti-tumor immune responses. The combination aims to overcome resistance mechanisms in tumors with high AHR activity by simultaneously inhibiting AHR-mediated immunosuppression and reactivating T-cell function via PD-1 blockade. The combination has shown early clinical activity in heavily pretreated patients with urothelial cancer and head and neck squamous cell carcinoma[1][2][3][4][5][8].